TY - JOUR TI - Cold protection allows local cryotherapy in a clinical-relevant model of traumatic optic neuropathy AU - Zhang, Yikui AU - Li, Mengyun AU - Yu, Bo AU - Lu, Shengjian AU - Zhang, Lujie AU - Zhu, Senmiao AU - Yu, Zhonghao AU - Xia, Tian AU - Huang, Haoliang AU - Jiang, WenHao AU - Zhang, Si AU - Sun, Lanfang AU - Ye, Qian AU - Sun, Jiaying AU - Zhu, Hui AU - Huang, Pingping AU - Hong, Huifeng AU - Yu, Shuaishuai AU - Li, Wenjie AU - Ai, Danni AU - Fan, Jingfan AU - Li, Wentao AU - Song, Hong AU - Xu, Lei AU - Chen, Xiwen AU - Chen, Tongke AU - Zhou, Meng AU - Ou, Jingxing AU - Yang, Jian AU - Li, Wei AU - Hu, Yang AU - Wu, Wencan A2 - Liton, Paloma B A2 - Zaidi, Mone A2 - Martinez, Alfredo VL - 11 PY - 2022 DA - 2022/03/30 SP - e75070 C1 - eLife 2022;11:e75070 DO - 10.7554/eLife.75070 UR - https://doi.org/10.7554/eLife.75070 AB - Therapeutic hypothermia (TH) is potentially an important therapy for central nervous system (CNS) trauma. However, its clinical application remains controversial, hampered by two major factors: (1) Many of the CNS injury sites, such as the optic nerve (ON), are deeply buried, preventing access for local TH. The alternative is to apply TH systemically, which significantly limits the applicable temperature range. (2) Even with possible access for ‘local refrigeration’, cold-induced cellular damage offsets the benefit of TH. Here we present a clinically translatable model of traumatic optic neuropathy (TON) by applying clinical trans-nasal endoscopic surgery to goats and non-human primates. This model faithfully recapitulates clinical features of TON such as the injury site (pre-chiasmatic ON), the spatiotemporal pattern of neural degeneration, and the accessibility of local treatments with large operating space. We also developed a computer program to simplify the endoscopic procedure and expand this model to other large animal species. Moreover, applying a cold-protective treatment, inspired by our previous hibernation research, enables us to deliver deep hypothermia (4 °C) locally to mitigate inflammation and metabolic stress (indicated by the transcriptomic changes after injury) without cold-induced cellular damage, and confers prominent neuroprotection both structurally and functionally. Intriguingly, neither treatment alone was effective, demonstrating that in situ deep hypothermia combined with cold protection constitutes a breakthrough for TH as a therapy for TON and other CNS traumas. KW - clinically relevant animal model KW - CNS trauma KW - cold protection KW - large animal model KW - local therapeutic hypothermia KW - traumatic optic neuropathy JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -